This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The first goal of this NHP program was to test the capacity of toll-like receptor (TLR) ligands to stimulate the innate immune system and thereby potentate effectiveness of an SIV Gag protein prime in potentiating the immunogenicity and efficacy of an Ad5/gag boost . As of this writing we have completed a 64 RM study of TLR4, TLR4, TLR7/8 and TLR9 activating adjuvants, alone and in combination, with gag protein. Both immunogenicity and efficacy against pathogenic SIV challenge were assessed. Data is currently being assembled manuscript(s) described our results is being prepared. A second study to investigate the immunogenicity and innate immune characteristics of Listeria/gag vectors in primates as a new prime for an AIDS vaccine prime/boost regimen was started in February 2009. 10 rhesus macaques with half of them exhibiting the Mamu-A*01 allele was enrolled. They were primed with Listeria-Gag vrs. empty Listeria and boosted with Ad5-gag. The priming efficacy of listeria seems to be little in comparison with the Gag protein formulated with TLR ligand adjuvant. A newly proposed experiment to determine efficacy of Rapamycin to improve the magnitude and quality of T-cell response to viral vectored SIV-antigens will start in February, 2010. The 10 RM from Listeria study will be re-enrolled and vaccinated with RhCMV/SIV vectors expressing SIV- RTN, Env, and Pol and then treated for 4 weeks with Rapamycin vs. control. We also in the final stages of planning for NHP vaccine efficacy trial that follows up on both the adjuvant results of our first experiment, and the successful Rv144 clinical trial of ALVAC prime/env protein boost vaccination. This will be an NHP efficacy trial of a pox vector prime and poly I:C adjuvanted env protein boost vaccine.